Genetic Variant PRXL2C:p.Leu110Val (chr9-96651483-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_153698.2(PRXL2C):c.328C>G(p.Leu110Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRXL2C
NM_153698.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31

Variant links:

Genes affected

PRXL2C (HGNC:16881): (peroxiredoxin like 2C) Predicted to enable antioxidant activity. Involved in positive regulation of ERK1 and ERK2 cascade and positive regulation of glycolytic process. [provided by Alliance of Genome Resources, Apr 2022]

PRXL2C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33777833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRXL2C	NM_153698.2 link	c.328C>G	p.Leu110Val	missense_variant	Exon 4 of 6	ENST00000375234.8	NP_714542.1	Q7RTV5
PRXL2C	XM_005251783.4 link	c.328C>G	p.Leu110Val	missense_variant	Exon 4 of 5		XP_005251840.1
PRXL2C	XM_005251784.5 link	c.166C>G	p.Leu56Val	missense_variant	Exon 4 of 6		XP_005251841.1	B7ZKK1
PRXL2C	XM_047422905.1 link	c.166C>G	p.Leu56Val	missense_variant	Exon 4 of 5		XP_047278861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRXL2C	ENST00000375234.8 link	c.328C>G	p.Leu110Val	missense_variant	Exon 4 of 6	1	NM_153698.2	ENSP00000364382.3	Q7RTV5
PRXL2C	ENST00000446045.1 link	c.187C>G	p.Leu63Val	missense_variant	Exon 4 of 6	1		ENSP00000398933.1	H0Y5J5
PRXL2C	ENST00000411939.5 link	c.109C>G	p.Leu37Val	missense_variant	Exon 3 of 4	3		ENSP00000412378.1	H0Y7F1
PRXL2C	ENST00000464512.1 link	n.335C>G		non_coding_transcript_exon_variant	Exon 3 of 4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245662

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457362

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724630

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000251

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.328C>G (p.L110V) alteration is located in exon 4 (coding exon 4) of the AAED1 gene. This alteration results from a C to G substitution at nucleotide position 328, causing the leucine (L) at amino acid position 110 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0027

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.014

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.75

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.2

REVEL

Benign

0.14

Sift

Benign

0.78

Sift4G

Benign

0.31

Polyphen

0.51

Vest4

0.55

MutPred

0.67

Gain of catalytic residue at L110 (P = 0.1812);

MVP

0.43

MPC

0.058

ClinPred

0.36

GERP RS

2.8

Varity_R

0.19

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over